Abstract The purpose of this proposal is to develop a highly biocompatible pulmonary assist device (PAD) to support patients with chronic lung disease for months to years. Over 12 million patients suffer from chronic lung disease in the US. These patients suffer from a gradual decline in respiratory function coupled with acute exacerbations that lead to a transient, but dangerous, worsening of their disease state. In the US, this results in over 700,000 hospital discharges per year, and approximately 180,000 deaths. Less than 2,000 of these patients will undergo lung transplantation, where 5-year survival is under 50%. For the remaining transplant ineligible patients, there is no means of destination therapy. The PAD is a compact, highly biocompatible gas exchanger for venovenous or venoarterial respiratory support lasting months to years. The PAD is coupled with a small ventricular assist device quality pump to allow for compact, mobile respiratory support. Our initial clinical goal is to use the PAD to move chronic lung disease patients from the ICU to the floor in an ambulatory bridge to transplant setting. After accomplishing this preliminary goal, the PAD system would transition toward destination therapy lasting years. During this time, the patient would be discharged home with planned monitoring and return to the hospital every 2-3 months for scheduled PAD replacement. Accordingly, the PAD must be designed with far greater biocompatibility than current oxygenators. Previous artificial lung designs from our lab have demonstrated minimal clot formation and no increase in resistance over two weeks of testing, despite using no anticoagulant coatings, by using an innovative gas exchange fiber bundle that slows clot formation and eliminates shear damage and activation of blood. The PAD will utilize a similar design while further improving biocompatibility by i) shrinking the device surface area and ii) utilizing a unique housing design that eliminates stagnant or recirculating flows. Lastly, the PAD is designed to operate with 1-2 modules. This allows for partial support during device replacement and allows for adjustment of support level based on the patient?s physiologic needs. With appropriate coating technology, a single device should function normally for months. This proposal will focus on prototyping and in vitro testing. The Phase I Specific Aims are to 1) determine PAD gas exchange and blood flow resistance, 2) quantify the blood damage of the PAD and compare to the Quadrox oxygenator, and 3) quantify the presence of blood flow stagnation in the PAD and compare it to the Quadrox. The success criteria are that a the PAD must: i) convert 2 L/min of venous blood to > 95% oxyhemoglobin saturation and transfer > 100 ml/min of CO2 with a single module, ii) have a blood flow resistance < 2.5 mmHg/(L/min) at 2 L/min of blood flow to a single module, iii) have lower or equal hemolysis and platelet consumption than the Quadrox when testing at 4 L/min of blood flow with 2 PAD modules in parallel, and iv) possess equal or superior dye washout than the Quadrox. Together, these results will position the PAD for success during long-term, Phase II testing.